Clinical studies have suggested a possible association of low serum vitamin D levels in patients with bone fractures. This, coupled with a high prevalence of fractures and increases in associated disability and mortality, begs the question, is there evidence to support a role for therapeutic drug monitoring of vitamin D levels to prevent bone fractures? We use a previously published nine-step decision-making algorithm to answer this question. Optimal dosages of vitamin D have not been determined, although daily intake guidelines are suggested. Current vitamin D assays yield varying results, making it challenging for clinicians to interpret results from clinical trials and apply them directly to patients and their specific serum level data. Fracture risk is not easily assessable clinically, with no clear relationship between vitamin D concentrations and bone mineral density. The existing primary literature shows no clear relationship between vitamin D concentrations and fracture risk; target concentrations are not well established. Although the pharmacokinetic parameters of vitamin D are unpredictable and vitamin D supplementation is frequently lifelong, results of a vitamin D assay are unlikely to make a significant difference in the clinical decision-making process (i.e., provide more information than clinical judgment alone). Most published studies on vitamin D levels and fracture risk did not control for other potential reasons to monitor levels, multifactorial risks for fractures, and other confounders. Given limited data to support a direct relation between vitamin D levels and clinical outcome of fracture, inconsistent between-assay results, and no consensus on optimal levels, there is insufficient evidence to recommend routine therapeutic drug monitoring of vitamin D for fracture prevention; however, other reasons for monitoring might exist that are beyond the scope of this review. Recent availability of vitamin D assay standards may lead to future improvements in comparability of research data, establishment of a target range, and interpretability of patient results.